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Context: Because of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease).Objective: To examine the evidence base and provide practical recommendations for evaluation, counseling, and etiologic treatment of patients with chronic T cruzi infection. Evidence Acquisition Literature review conducted based on a systematic MEDLINE search for all available years through 2007; review of additional articles, reports, and book chapters; and input from experts in the field.Evidence Synthesis: The patient newly diagnosed with Chagas disease should undergo a medical history, physical examination, and resting 12-lead electrocardiogram (ECG) with a 30-second lead II rhythm strip. If this evaluation is normal, no further testing is indicated; history, physical examination, and ECG should be repeated annually. If findings suggest Chagas heart disease, a comprehensive cardiac evaluation, including 24-hour ambulatory ECG monitoring, echocardiography, and exercise testing, is recommended. If gastrointestinal tract symptoms are present, barium contrast studies should be performed. Antitrypanosomal treatment is recommended for all cases of acute and congenital Chagas disease, reactivated infection, and chronic T cruzi infection in individuals 18 years or younger. In adults aged 19 to 50 years without advanced heart disease, etiologic treatment may slow development and progression of cardiomyopathy and should generally be offered; treatment is considered optional for those older than 50 years. Individualized treatment decisions for adults should balance the potential benefit, prolonged course, and frequent adverse effects of the drugs. Strong consideration should be given to treatment of previously untreated patients with human immunodeficiency virus infection or those expecting to undergo organ transplantation.Conclusions: Chagas disease presents an increasing challenge for clinicians in the United States. Despite gaps in the evidence base, current knowledge is sufficient to make practical recommendations to guide appropriate evaluation, management, and etiologic treatment of Chagas disease. [ABSTRACT FROM AUTHOR]

Epidemics of visceral leishmaniasis (VL) in major Brazilian cities are new phenomena since 1980. As determinants of transmission in urban settings probably operate at different geographic scales, and information is not available for each scale, a multilevel approach was used to examine the effect of canine infection and environmental and socio-economic factors on the spatial variability of incidence rates of VL in the city of Teresina. Details on an outbreak of greater than 1200 cases of VL in Teresina during 1993-1996 were available at two hierarchical levels: census tracts (socio-economic characteristics, incidence rates of human VL) and districts, which encompass census tracts (prevalence of canine infection). Remotely sensed data obtained by satellite generated environmental information at both levels. Data from census tracts and districts were analysed simultaneously by multilevel modelling. Poor socio-economic conditions and increased vegetation were associated with a high incidence of human VL. Increasing prevalence of canine infection also predicted a high incidence of human VL, as did high prevalence of canine infection before and during the epidemic. Poor socio-economic conditions had an amplifying effect on the association between canine infection and the incidence of human VL. Focusing interventions on areas with characteristics identified by multilevel analysis could be a cost-effective strategy for controlling VL. Because risk factors for infectious diseases operate simultaneously at several levels and ecological data usually are available at different geographical scales, multilevel modelling is a valuable tool for epidemiological investigation of disease transmission. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) or kala-azar (KA) affects the rural poor, causing significant morbidity and mortality. We examined the epidemiological and social impact of KA in an affected village in Bangladesh. A population-based survey of the village residents showed a case fatality rate of 14.7% among females and 5.3% among males. Before initiation of the study, female patients were ill longer than males before they received treatment. Future work needs to focus on understanding the implications of KA on women and to develop sustainable strategies for appropriate and timely access to treatment. [ABSTRACT FROM AUTHOR]

A 10-year old female on phenytoin therapy developed a rash and lymphadenopathy. H.p.l.c. assays of urinary metabolites indicated no differences in stereoselective metabolism of phenytoin to phenolic and dihydrodiol metabolites as compared with volunteers given the drug or with pediatric patients without adverse reactions. This suggests that no obvious difference in stereoselective metabolism of phenytoin to potentially toxic arene oxides exists between this patient and other patients on phenytoin. Our results are consistent with the hypothesis that differences in peripheral detoxication of phenytoin arene oxides and not differences in hepatic metabolism of phenytoin may be responsible for such adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Babesiosis poses significant risks of adverse outcomes in individuals with immunocompromising conditions (IC) and asplenia/hyposplenia (AH). This study compares clinical outcomes between these vulnerable groups and immunocompetent patients., Methods: A multicenter retrospective cohort study included adult patients with laboratory-confirmed babesiosis from 2009 to 2023. Complications, management, and outcomes were compared between patients with IC/AH (ICAH) and without ICAH (immune intact cohort)., Results: Of 225 patients (mean age 66 years, 36% female), 112 were ICAH. ICAH patients had higher median peak parasitemia (2.8% vs. 0.9%, p<0.0001) and higher rates of complications, including acute kidney injury (24% vs. 11%, p=0.016), acute respiratory distress syndrome (11% vs. 4%, p=0.041), and were more likely to undergo packed red blood cell transfusion (31% vs. 17%, p=0.023) and exchange transfusion (18% vs. 6%, p=0.008). Treatment duration was longer in the ICAH cohort (median 27 vs. 10 days, p<0.001), particularly in those with both IC and AH (median 43 days, p=0.003). ICAH patients had higher 12-month all-cause mortality (7% vs. 1%, p=0.019) and recurrence rates (8% vs. 0%, p=0.001). Hematologic malignancy (OR=7.0, p=0.023) and B-cell-depleting therapies (OR=9.4, p=0.015) were significant predictors of recurrence. Despite most patients undergoing follow-up testing with blood smears and PCR, these did not reliably predict recurrence., Conclusion: Patients with ICAH with babesiosis experience more severe disease and higher complication rates. Follow-up testing, including blood smear and PCR, did not reliably predict recurrence, highlighting the need for more effective monitoring strategies in these high-risk populations., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.

Background: Chagas disease affects an estimated 326 000-347 000 people in the United States and is severely underdiagnosed. Lack of awareness and clarity regarding screening and diagnosis is a key barrier. This article provides straightforward recommendations, with the goal of simplifying identification and testing of people at risk for US healthcare providers., Methods: A multidisciplinary working group of clinicians and researchers with expertise in Chagas disease agreed on 6 main questions, and developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, after reviewing the relevant literature on Chagas disease in the United States., Results: Individuals who were born or resided for prolonged time periods in endemic countries of Mexico and Central and South America should be tested for Trypanosoma cruzi infection, and family members of people who test positive should be screened. Women of childbearing age with risk factors and infants born to seropositive mothers deserve special consideration due to the risk of vertical transmission. Diagnostic testing for chronic T. cruzi infection should be conducted using 2 distinct assays., Conclusions: Increasing provider-directed screening for T. cruzi infection is key to addressing this neglected public health challenge in the United States., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

We studied 2351 participants with coronavirus disease 2019; 1177 (50%) reported previous dengue infection. Those without previous dengue had a higher risk of death (hazard ratio: .44; 95% confidence interval: .22-.89; P = .023) in 60-day follow-up. These findings raise the possibility that dengue might induce immunological protection against severe acute respiratory syndrome coronavirus 2., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Case: We describe the case of a 74-year-old man who developed severe hip pain several days after an intra-articular methylprednisolone injection to his right hip. Culture of the ipsilateral iliopsoas bursa revealed a Staphylococcus lugdunensis infection, which was successfully eradicated through irrigation and debridement as well as antibiotics., Conclusion: Infection after hip injection is a known theoretical risk but is rarely reported in the literature. We present a case of septic bursitis after corticosteroid injection. Readers should be mindful that these complications do occur in clinical practice and portend significant morbidity., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B514)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0-4.0%). Lethality rates have declined over time (P = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Prosthetic joint infection (PJI) is a morbid complication following total joint arthroplasty (TJA). PJI diagnosis and treatment has changed over time, and patient co-management with a high-volume musculoskeletal infectious disease (MSK ID) specialist has been implemented at our institution in the last decade., Methods: We retrospectively evaluated all consecutive TJA patients treated for PJI between 1995 and 2018 by a single high-volume revision TJA surgeon. Microbial identities, antibiotic resistance, prior PJI, and MSK ID consultation were investigated., Results: In total, 261 PJI patients (median age 66 years, interquartile range 57-75) were treated. One-year and 5-year reinfection rates were 15.8% (95% confidence interval [CI] 11.6-20.7) and 22.1% (95% CI 17.0-27.7), respectively. Microbial identities and antibiotic resistances did not change significantly over time. Despite seeing more prior PJI patients (53.3% vs 37.6%, P = .012), MSK ID-managed patients had similar infection rates as non-MSK ID-managed patients (hazard ratio [HR] 1.02, 95% CI 0.6-1.75, P = .93). Prior PJI was associated with higher reinfection risk (HR 2.39, 95% CI 1.39-4.12, P = .002) overall and in patients without MSK ID consultation, specifically (HR 2.78, 95% CI 1.37-5.65, P = .005). This risk was somewhat lower and did not reach significance in prior PJI patients with MSK ID consultation (HR 1.97, 95% CI 0.87-4.48, P = .106)., Conclusion: We noted minimal differences in microbial/antibiotic resistances for PJI over 20 years in a single institution, suggesting current standards of PJI treatment remain encouragingly valid in most cases. MSK ID involvement was not associated with lower reinfection risk overall; however, in patients with prior PJI, the risk of reinfection appeared to be somewhat lower with MSK ID involvement., Level of Evidence: Level IV-Case Series., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Disseminated cutaneous leishmaniasis (DCL) is an uncommon form of Leishmania braziliensis infection. It remains unknown why some people develop this clinical condition. We describe 14 DCL patients in Northeast Brazil during 2015-2018. These patients regularly drank large amounts of alcohol, possibly increasing their risk for DCL.

Background: Knee arthrodesis (KA) and above-knee amputation (AKA) have been used for salvage of failed total knee arthroplasty (TKA) after periprosthetic joint infection (PJI). However, few studies have assessed the outcomes of KA after TKA PJI, as it remains an uncommon procedure. We investigated rates of AKA, control of infection, and ambulatory status after KA for TKA PJI treatment., Methods: This was a retrospective and single-surgeon series of 51 failed TKAs due to PJI treated with two-stage KA between 2000 and 2016 with a minimum of 2-year follow-up. Patient demographics, comorbidities, surgical history, radiographic data, and outcomes of KA treatment were recorded., Results: Infection was successfully controlled in 48 of 51 patients (94.1%); of these, 24 knees (50.0%) required no reoperation subsequent to the index KA, whereas the remaining 24 (50.0%) patients required a median of 1 additional operation. Nonunion, malunion, or delayed union was noted in 10 patients (19.6%). Of the 48 patients who were successfully treated with KA, 41 patients (85.4%) remained ambulatory after KA and 9 of these patients (18.8%) did not require assistive devices. Three of 51 patients (5.9%) progressed to AKA after KA., Conclusion: Patients undergoing KA for TKA PJI had high rates of infection control and preservation of ambulatory status, with low rates of progression to AKA in our study., Level of Evidence: Level IV-case series., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Approximately 300,000 persons in the United States (US) are infected with Trypanosoma cruzi, the protozoan that causes Chagas disease, but less than 1% are estimated to have received antiparasitic treatment. Benznidazole was approved by the US Food and Drug Administration (FDA) for treatment of T. cruzi infection in 2017 and commercialized in May 2018. This paper analyzes factors that affect access to benznidazole following commercialization and suggests directions for future actions to expand access. We applied an access framework to identify barriers, facilitators, and key actors that influence the ability of people with Chagas disease to receive appropriate treatment with benznidazole. Data were collected from the published literature, key informants, and commercial databases. We found that the mean number of persons who obtained benznidazole increased from just under 5 when distributed by the CDC to 13 per month after the commercial launch (from May 2018 to February 2019). Nine key barriers to access were identified: lack of multi-sector coordination, failure of health care providers to use a specific order form, lack of an emergency delivery system, high medical costs for uninsured patients, narrow indications for use of benznidazole, lack of treatment guidelines, limited number of qualified treaters, difficulties for patients to make medical appointments, and inadequate evaluation by providers to determine eligibility for treatment. Our analysis shows that access to benznidazole is still limited after FDA approval. We suggest six areas for strategic action for the pharmaceutical company that markets benznidazole and its allied private foundation to expand access to benznidazole in the US. In addition, we recommend expanding the existing researcher-clinician network by including government agencies, companies and others. This paper's approach could be applied to access programs for benznidazole in other countries or for other health products that target neglected populations throughout the world., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following potential competing interests. KY was a graduate student at the Harvard T.H. Chan School of Public Health and this study was a part of his doctoral project financially sponsored by Fundación Mundo Sano. MRR received a grant from Fundación Mundo Sano to organize a workshop titled “Rethinking Chagas” at the Harvard T.H. Chan School of Public Health, Boston, on October 22, 2018." This paper represents the work of the authors and should not be taken as representing either FMS or Exeltis USA. JMG was supported by Grant Number T32 AI007433 from the National Institute of Allergy and Infectious Diseases. The contents of this research are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Trypanosoma cruzi is the etiological agent of Chagas disease, usually transmitted by triatomine vectors. An estimated 20 to 30% of infected individuals develop potentially lethal cardiac or gastrointestinal disease. Sylvatic transmission cycles exist in the southern United States, involving 11 triatomine vector species and infected mammals such as rodents, opossums, and dogs. Nevertheless, imported chronic T. cruzi infections in migrants from Latin America vastly outnumber locally acquired human cases. Benznidazole is now FDA approved, and clinical and public health efforts are under way by researchers and health departments in a number of states. Making progress will require efforts to improve awareness among providers and patients, data on diagnostic test performance and expanded availability of confirmatory testing, and evidence-based strategies to improve access to appropriate management of Chagas disease in the United States., (Copyright © 2019 American Society for Microbiology.)

A 61-year-old woman with a right total knee arthroplasty presented with 1 week of atraumatic right knee swelling, pain, and fevers 2 weeks following a routine screening colonoscopy. Aspiration was concerning for prosthetic joint infection and she underwent definitive treatment with irrigation and debridement with polyethylene exchange followed by a 6-week course of oral metronidazole. Cultures speciated as Bacteroides fragilis with the presumed source being the colonoscopy causing transient bacteremia and subsequent seeding of the right knee. This case highlights the need for consideration of guidelines regarding prophylactic antibiotics to prevent prosthetic joint infection after endoscopic procedures., (© 2019 The Authors.)

Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (P<0.001) and had positive direct antiglobulin tests for IgG and complement component 3; warm autoantibodies were identified in all these patients. No alternative explanation for clinical hemolysis was found. WAHA required immunosuppressive treatment in 4 of the 6 patients. Conclusions We documented post-babesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.

Background: "Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States., Objectives: The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively., Methods: A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures., Results: Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution., Conclusions: We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios., Level of Evidence: 5 Therapeutic., (© 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings., Methodology/principal Findings: We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort., Conclusions/significance: Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service responsiveness with thoughtful strategies and management practices in the local health systems.

Background: To evaluate the effect of insecticide spraying for vector control and elimination of infected dogs on the incidence of human infection with L. infantum, a randomized community intervention trial was carried out in the city of Teresina, Brazil., Methods/principal Findings: Within each of ten localities in the city, four blocks were selected and randomized to 4 interventions: 1) spraying houses and animal pens with insecticide; 2) eliminating infected dogs; 3) combination of spraying and eliminating dogs, and 4) nothing. The main outcome is the incidence of infection assessed by the conversion of the Montenegro skin test (MST) after 18 months of follow-up in residents aged ≥ 1 year with no previous history of visceral leishmaniasis (VL). Reactions were measured at 48-72 h, induration of ≥ 5 mm considered positive. Interventions were executed after the baseline interview and repeated 6 and 12 months later. The effects of each type of intervention scheme on the incidence of infection were assessed by calculating relative risks and 95% confidence intervals using Poisson population-averaged regression models with robust variance. Among the 1105 participants, 408 (37%) were MST positive at baseline. Of the 697 negatives, only 423 (61%) were reexamined at the end of the follow-up; 151 (36%) of them converted to a positive MST. Only dog culling had some statistically significant effect on reducing the incidence of infection, with estimates of effectiveness varying between 27% and 52%, depending on the type of analysis performed., Conclusions/significance: In light of the continuous spread of VL in Brazil despite the large scale deployment of insecticide spraying and dog culling, the relatively low to moderate effectiveness of dog culling and the non-significant effect of insecticide spraying on the incidence of human infection, we conclude that there is an urgent need for revision of the Brazilian VL control program.

We conducted active surveillance for kala-azar and post-kala-azar dermal leishmaniasis (PKDL) in a population of 24,814 individuals. Between 2002 and 2010, 1,002 kala-azar and 185 PKDL cases occurred. Median PKDL patient age was 12 years; 9% had no antecedent kala-azar. Cases per 10,000 person-years peaked at 90 for kala-azar (2005) and 28 for PKDL (2007). Cumulative PKDL incidence among kala-azar patients was 17% by 5 years. Kala-azar patients younger than 15 years were more likely than older patients to develop PKDL; no other risk factors were identified. The most common lesions were hypopigmented macules. Of 98 untreated PKDL patients, 48 (49%) patients had resolution, with median time of 19 months. Kala-azar patients showed elevated interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and interleukin 10 (IL-10). Matrix metalloproteinase 9 (MMP9) and MMP9/tissue inhibitor of matrix metalloproteinase-1 (TIMP1) ratio were significantly higher in PKDL patients than in other groups. PKDL is frequent in Bangladesh and poses a challenge to the current visceral leishmaniasis elimination initiative in the Indian subcontinent.

Background: In epidemiologic research, incidence is often estimated from data arising from an imperfect diagnostic test performed at unequally spaced intervals over time., Methods: We developed a likelihood-based method to estimate incidence when disease status is measured imperfectly and assays are performed at multiple unequally spaced visits. We assumed conditional independence, no remission, known constant levels of sensitivity and specificity, and constant incidence rates over time. The method performance was evaluated by examining its bias, accuracy (i.e., mean squared error (MSE)), and coverage probability in a simulation study of 4000 datasets, and then we applied the proposed method to a study of hepatitis C virus (HCV) infection in a cohort of pregnant women in the period 1997-2006., Results: The simulation revealed that our method has minimal bias and low MSE, as well as good coverage probability of the resulting confidence intervals. In the application to HCV study, the standard incidence rate estimate which ignores the imperfections of the diagnostic test (number of events/person-years), was 13.7 new HCV cases per 1000 person-years (95% confidence interval 10.1, 17.4). The adjusted incidence estimates (obtained using our proposed method) ranged from 0.4 cases per 1000 person-years (when sensitivity and specificity were assumed to both be 95%) to 13.7 cases per 1000 person-years (when sensitivity and specificity were both 100%). The magnitude of difference between standard and adjusted estimates varied depending on specificity and sensitivity assumptions. Specificity had the greatest impact on the magnitude of bias., Conclusions: Scientists should be aware of the impact of misclassification on incidence estimates. Appropriate study design, proper selection of the diagnostic test, and adjustment for misclassification probabilities in the analysis is necessary to obtain the most accurate incidence estimates., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20-30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections.

Background: The probability of contracting malaria in a given individual is determined not only by the individual's characteristics, but also the ecological factors that characterize the level of human-vector contact in the population. Examination of the relationship between "individual" and "supra-individual" variables over time is important for understanding the local malaria epidemiology. This is essential for planning effective intervention strategies specifically for each location., Methods: A retrospective cohort study was conducted, which followed a community-cohort of about 3,500 residents in seven hamlets along the Thai-Myanmar border between 1999 and 2006. Potential malaria determinants measured at different levels (temporal variables, individual variables, and hamlet variables) were incorporated into multilevel models to estimate their effects on an individual's risk of malaria attack., Results: The monthly minimum temperature was significantly associated with the seasonal variation of malaria risk. An individual risk of malaria attack decreased by about 50% during the period that active surveillance was conducted; an additional 15% and 25% reduction of Plasmodium falciparum and Plasmodium vivax incidence, respectively, was observed after the use of artesunate-mefloquine combination therapy (ACT) for treatment of P. falciparum. Male children (age < 16 years old) were at highest risk of both P. falciparum and P. vivax attack. An increase in the hamlet's incidence of P. falciparum and P. vivax by 1 per 100 persons in a previous month resulted in 1.14 and 1.34 times increase in the risk of P. falciparum and P. vivax, respectively, among individuals in a particular hamlet., Conclusion: In a small area with low malaria transmission intensity, the variation in mosquito abundance is relatively similar across the residential areas; incidence of malaria between hamlets, which reflects the community level of human infectious reservoirs, is an important predictor for the malaria risk among individuals within these hamlets. Therefore, local malaria control strategies should focus on interventions that aim to reduce the gametocyte carriage in the population, such as early detection and treatment programmes and the use of ACT for P. falciparum.

Background: We conducted a study of congenital Trypanosoma cruzi infection in Santa Cruz, Bolivia. Our objective was to apply new tools to identify weak points in current screening algorithms, and find ways to improve them., Methods: Women presenting for delivery were screened by rapid and conventional serological tests. For infants of infected mothers, blood specimens obtained on days 0, 7, 21, 30, 90, 180, and 270 were concentrated and examined microscopically; serological tests were performed for the day 90, 180, and 270 specimens. Maternal and infant specimens, including umbilical tissue, were tested by polymerase chain reaction (PCR) targeting the kinetoplast minicircle and by quantitative PCR., Results: Of 530 women, 154 (29%) were seropositive. Ten infants had congenital T. cruzi infection. Only 4 infants had positive results of microscopy evaluation in the first month, and none had positive cord blood microscopy results. PCR results were positive for 6 (67%) of 9 cord blood and 7 (87.5%) of 8 umbilical tissue specimens. PCR-positive women were more likely to transmit T. cruzi than were seropositive women with negative PCR results (P < .05). Parasite loads determined by quantitative PCR were higher for mothers of infected infants than for seropositive mothers of uninfected infants P < .01). Despite intensive efforts, only 58% of at-risk infants had a month 9 specimen collected., Conclusions: On the basis of the low sensitivity of microscopy in cord blood and high rate of loss to follow-up, we estimate that current screening programs miss one-half of all infected infants. Molecular techniques may improve early detection.

This review is a general discussion of common zoonotic infections of companion animals in the United States. Microbes, routes of transmission, and risks to immunocompromised persons are discussed. The primary focus of this article is dogs and cats, although zoonoses of avian, rodent, and rabbit companion animals are discussed in brief. An awareness of zoonoses will allow veterinarians and physicians to collaboratively prevent transmission and treat clinical disease in both human and veterinary patients.

Background: Effective malaria control has successfully reduced the malaria burden in many countries, but to eliminate malaria, these countries will need to further improve their control efforts. Here, a malaria control programme was critically evaluated in a very low-endemicity Thai-Myanmar border population, where early detection and prompt treatment have substantially reduced, though not ended, Plasmodium falciparum transmission, in part due to carriage of late-maturing gametocytes that remain post-treatment. To counter this effect, the WHO recommends the use of a single oral dose of primaquine along with an effective blood schizonticide. However, while the effectiveness of primaquine as a gametocidal agent is widely documented, the mismatch between primaquine's short half-life, the long-delay for gametocyte maturation and the proper timing of primaquine administration have not been studied., Methods: Mathematical models were constructed to simulate 8-year surveillance data, between 1999 and 2006, of seven villages along the Thai-Myanmar border. A simple model was developed to consider primaquine pharmacokinetics and pharmacodynamics, gametocyte carriage, and infectivity., Results: In these populations, transmission intensity is very low, so the P. falciparum parasite rate is strongly linked to imported malaria and to the fraction of cases not treated. Given a 3.6-day half-life of gametocyte, the estimated duration of infectiousness would be reduced by 10 days for every 10-fold reduction in initial gametocyte densities. Infectiousness from mature gametocytes would last two to four weeks and sustain some transmission, depending on the initial parasite densities, but the residual mature gametocytes could be eliminated by primaquine. Because of the short half-life of primaquine (approximately eight hours), it was immediately obvious that with early administration (within three days after an acute attack), primaquine would not be present when mature gametocytes emerged eight days after the appearance of asexual blood-stage parasites. A model of optimal timing suggests that primaquine follow-up approximately eight days after a clinical episode could further reduce the duration of infectiousness from two to four weeks down to a few days. The prospects of malaria elimination would be substantially improved by changing the timing of primaquine administration and combining this with effective detection and management of imported malaria cases. The value of using primaquine to reduce residual gametocyte densities and to reduce malaria transmission was considered in the context of a malaria transmission model; the added benefit of the primaquine follow-up treatment would be relatively large only if a high fraction of patients (>95%) are initially treated with schizonticidal agents., Conclusion: Mathematical models have previously identified the long duration of P. falciparum asexual blood-stage infections as a critical point in maintaining malaria transmission, but infectiousness can persist for two to four weeks because of residual populations of mature gametocytes. Simulations from new models suggest that, in areas where a large fraction of malaria cases are treated, curing the asexual parasitaemia in a primary infection, and curing mature gametocyte infections with an eight-day follow-up treatment with primaquine have approximately the same proportional effects on reducing the infectious period. Changing the timing of primaquine administration would, in all likelihood, interrupt transmission in this area with very good health systems and with very low endemicity.

Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting.

As part of the global effort to eradicate dracunculiasis (Guinea worm disease), several endemic countries established case containment centers to provide treatment and support to patients with emerging Guinea worms to keep them from contaminating water sources. To assess the functioning, effectiveness, and public perception of this intervention, we visited eight centers and conducted surveys in 32 villages in Togo and Ghana. In the areas served by these centers, incidence dropped by 71% in Togo and 42% in Ghana from 2003 to 2004. Among persons with emerging worms, admission to the centers was associated with younger age (P value = 0.04) after controlling for occupation and gender. Overall, the centers functioned well and were regarded favorably: 99% of the 152 center-attendees expressed satisfaction with their stay. Strategically-located case containment centers in conjunction with other interventions appear to play an important role in the final effort to eradicate dracunculiasis.

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

We evaluated the effectiveness of an overseas pre-departure regimen of five days of albendazole for presumptive treatment of intestinal parasites by examining stool specimens in treated and untreated Montagnard refugees after arrival in the United States. Among 815 refugees evaluated, fully treated refugees had a significantly lower prevalence of helminths (11 [1.4%] of 777), specifically hookworm and Ascaris lumbricoides, than untreated pregnant women (3 [20%] of 15) (P < 0.001). Multivariate analysis showed that treatment was associated with significantly lower rates of infection with helminths but not protozoa. Post-arrival gastrointestinal symptoms were not associated with findings on stool examination. Our evaluation suggests that although additional studies are needed to determine optimal treatment regimens for intestinal parasites, especially among young children and pregnant women, a five-day course of pre-departure albendazole was effective in reducing helminthic infection in treated refugees.

Among parasitic diseases, morbidity and mortality caused by leishmaniasis are surpassed only by malaria and lymphatic filariasis. However, estimation of the leishmaniasis disease burden is challenging, due to clinical and epidemiological diversity, marked geographic clustering, and lack of reliable data on incidence, duration, and impact of the various disease syndromes. Non-health effects such as impoverishment, disfigurement, and stigma add to the burden, and introduce further complexities. Leishmaniasis occurs globally, but has disproportionate impact in the Horn of Africa, South Asia and Brazil (for visceral leishmaniasis), and Latin America, Central Asia, and southwestern Asia (for cutaneous leishmaniasis). Disease characteristics and challenges for control are reviewed for each of these foci. We recommend review of reliable secondary data sources and collection of baseline active survey data to improve current disease burden estimates, plus the improvement or establishment of effective surveillance systems to monitor the impact of control efforts.

Background: Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy., Methods and Findings: We performed a serological survey in children 2-18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4-7.9]) children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC) plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children., Conclusions: We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

Background: Schistosomiasis and strongyloidiasis cause substantial morbidity and mortality among hundreds of millions of infected persons worldwide. In the United States, these infections are most commonly found among international travelers, immigrants, and refugees from areas of endemicity. Refugees resettled to the United States since 2000 include >3800 "Lost Boys and Girls" of Sudan and 8000 Somali Bantu. Many Lost Boys and Girls of Sudan reported chronic abdominal pain only since arrival, and some received diagnoses of schistosomiasis or strongyloidiasis. We assessed seroprevalence of these infections among these refugees and hypothesized an association between infection and abdominal pain., Methods: We offered a survey assessing chronic abdominal pain and serologic testing for schistosomiasis and strongyloidiasis to all 800 attendees of a Lost Boys and Girls of Sudan reunion in the United States. Serologic testing was performed on preimmigration specimens obtained from 100 United States-bound Somali Bantu refugees., Results: Of the 462 Sudanese refugees (58%) tested, 44% and 46% were seropositive for schistosomiasis (primarily due to Schistosoma mansoni) and strongyloidiasis, respectively; 24% of those who tested positive for schistosomiasis had S. mansoni antigenemia. Forty-six percent reported chronic abdominal pain, which was not associated with either infection. Among 100 Somali Bantu, 73% and 23% tested seropositive for schistosomiasis (primarily due to Schistosoma haematobium) and strongyloidiasis, respectively., Conclusions: The high seroprevalence of schistosomiasis and strongyloidiasis among Sudanese Lost Boys and Girls and Somali Bantu refugees supports presumptive treatment for these refugees. Current refugee resettlement policies inadequately address these diseases; our data support consideration of predeparture presumptive therapy for all refugees from areas of endemicity.